EGFR mutation + PIK3CA mutation

EGFR over-expression, rather than PTEN loss or PIK3CA mutations, may contribute to PI3K/AKT pathway dysregulation in canine STS. Further studies with larger sample sizes and additional validation techniques are necessary to confirm these findings.

AXL and PIM-1 expression detected in CTCs during treatment suggesting new possible therapeutic strategies. Our results reveal that comprehensive liquid biopsy analysis can efficiently represent the heterogeneous molecular landscape and provide prominent information on subsequent treatments for NSCLC patients at PD since druggable molecular alterations were detected in CTCs.

Patients with ALK mutant, BRAF mutant or NRAS mutant were more prone to metastasis, while the HER 2 mutation group was less metastatic. Patients with EGFR mutant NSCLC are more likely to develop bone, lung, or brain metastasis.

We also studied preclinical Ba/F3 models expressing EGFR -K745_E746insIPVAIK (Ba/F3-IPVAIK) and EGFR -delE746_A750 (Ba/F3-Del19) to investigate the sensitivity to 1st-generation (gen) (gefitinib and erlotinib), 2nd-gen (afatinib, dacomitinib, and poziotinib), 3rd-gen (osimertinib), and EGFR exon 20 insertion active TKIs (mobocertinib, sunvozertinib, and zipalertinib). The preclinical therapeutic window of Ba/F3-IPVAIK and Ba/F3-Del19 for all the 2nd generation TKIs were similarly favorable, whereas Ba/F3-IPVAIK had much unfavorable therapeutic windows to other EGFR-TKIs compared to Ba/F3-Del19. Conclusions : Our clinical and preclinical findings indicate 2nd-gen EGFR-TKIs are more effective than 1st and 3rd-gen EGFR-TKIs in patients with EGFR exon 19 insertions.

Mutation profiles differed by histological type and metastases status and were significantly associated with PD-L1 expression. In the context of limited resources, our results may help prioritize patient for testing when tissue material and funding is limited.

We highlight the role of PIK3CA mutation as an acquired resistance mechanism against EGFR-TKIs in EGFR-mutant NSCLC. Crucially, we explore therapeutic strategies targeting PIK3CA-mediated resistance to EGFR TKIs in lung cancer, aiming to optimize the effectiveness of treatment.

Furthermore, additional EGFR resistance mutations, such as C797S, were 1 case. Expected Conclusions MET amp and PIK3CA mutation are the common resistance mechanisms of osimertinib PD, and the rate of additional EGFR resistance mutations is lower compared with prior studies.

In breast cancer (n=22), relevant alterations included ERBB2 amp (22%) and mutations in PIK3CA (43%), ESR1 (4.8%), ERBB2 (4.8%) and BRCA1/2 (4.8%). Conclusions This analysis of the first tumor samples tested by a new CGP panel in AME demonstrated detection of actionable alterations at the expected frequency with only 15 days median TAT.

The liquid-first approach enhances the yield of rare mutations by tissue NGS which is resource-dependent. It benefits regions where tissue biopsy is a rate limiting factor and EGFR mutations are prevalent.

HCC CK19+/CK7+ targeted therapy might benefit from a CTNNB1, TP53, ALK, EGFR, MAP2K2, RET, PTEN, and IDH2 panel, standardized for PLC spectrum. This knowledge would allow better understanding the clinical course and PLC heterogeneity, together with improving tumor classification and treatment.

Moreover, the combined effect and mechanism of gefitinib and BYL719 were also confirmed in the NSCLC cells and patient-derived organoids under 3D culture condition, as well as in vivo. Taken together, the data indicate that PIK3CA mutation induces more aggressive growth and gefitinib resistance in NSCLC cells, and the combination treatment with gefitinib and BYL719 is a promising therapeutic approach to overcoming EGFR-TKIs resistance induced by PI3K/AKT activation.

Although no statistical significance was found between the detected mutation and clinicopathological data, it was concluded that PDGFRA mutation might be associated with advanced-stage disease development. This study's findings regarding different molecular types of UCS and information on oncogenesis of UCS can provide inferences for targeted therapies in the future by identifying targetable mutations representing early oncogenic events and thereby contribute toward further studies on this subject.